Pentacyclic Triterpenoid Phytochemicals with Anticancer Activity: Updated Studies on Mechanisms and Targeted Delivery.

Pentacyclic triterpenoids (TTs) represent a unique family of phytochemicals with interesting properties and pharmacological effects, with some representatives, such as betulinic acid (BA) and betulin (B), being mainly investigated as potential anticancer molecules. Considering the recent scientific and preclinical investigations, a review of their anticancer mechanisms, structure-related activity, and efficiency improved by their insertion in nanolipid vehicles for targeted delivery is presented. A systematic literature study about their effects on tumor cells in vitro and in vivo, as free molecules or encapsulated in liposomes or nanolipids, is discussed. A special approach is given to liposome-TTs and nanolipid-TTs complexes to be linked to microbubbles, known as contrast agents in ultrasonography. The production of such supramolecular conjugates to deliver the drugs to target cells via sonoporation represents a new scientific and applicative direction to improve TT efficiency, considering that they have limited availability as lipophilic molecules. Relevant and recent examples of in vitro and in vivo studies, as well as the challenges for the next steps towards the application of these complex delivery systems to tumor cells, are discussed, as are the challenges for the next steps towards the application of targeted delivery to tumor cells, opening new directions for innovative nanotechnological solutions.

Pharmacological Property and Cytotoxic Effect Showing Antiproliferative Potency in Human Melanoma Cell Lines (A375) of Combretum racemosum P. Beauv. Leaf and Root Extracts Used in Benin.

Combretum racemosum, a plant from the Combretaceae family, is traditionally used in Benin for various health problems. However, scientific research on Beninese samples of this plant is limited. The aim of this study was to identify and assess the bioactive compounds in the plant's leaves and roots. Initial screening involved analyzing powders derived from these parts for total polyphenols, flavonoids, and both condensed and hydrolyzable tannins. The polyphenolic compounds were analyzed using HPLC-DAD-ESI-MS. To evaluate the plant's antimicrobial properties, the agar diffusion method was employed, while FRAP and DPPH assays were used to determine its antioxidant capacity. For anti-inflammatory activity, the study utilized tests for in vitro protein denaturation inhibition and in vivo acute edema induced by carrageenan. Additionally, an antiproliferative assay was conducted using the human melanoma cell line A375. The analysis revealed the presence of significant polyphenolic compounds in both the leaf and root extracts of C. racemosum. Notably, compounds like Pedunculagin, Vescalagin, Casuarictin, and Digalloyl-glucoside were abundant in the leaves, with Vescalagin being especially predominant in the roots. The study also found that the dichloromethane extracts from the leaves and roots exhibited bactericidal effects on a substantial percentage of meat-isolated strains. Moreover, the antioxidant activities of these extracts were confirmed through FRAP and DPPH methods. Interestingly, the dichloromethane root extract showed strong activity in inhibiting thermal albumin denaturation, while the water-ethanol leaf extract demonstrated significant edema inhibition. Finally, the study observed that C. racemosum extracts reduced cell viability in a dose-dependent manner, with leaf extracts showing more pronounced antiproliferative effects than root extracts. These findings highlight the potential of C. racemosum leaves and roots as sources of compounds with diverse and significant biological activities. In conclusion, C. racemosum's leaves and roots exhibit promising biological activities, highlighting their potential medicinal value.

Enhanced Cytotoxicity and Antimelanoma Activity of Novel Semisynthetic Derivatives of Betulinic Acid with Indole Conjugation.

The prevalence and severity of skin cancer, specifically malignant melanoma, among Caucasians remains a significant concern. Natural compounds from plants have long been explored as potential anticancer agents. Betulinic acid (BI) has shown promise in its therapeutic properties, including its anticancer effects. However, its limited bioavailability has hindered its medicinal applications. To address this issue, two recently synthesized semisynthetic derivatives, N-(2,3-indolo-betulinoyl)diglycylglycine (BA1) and N-(2,3-indolo-betulinoyl)glycylglycine (BA2), were compared with previously reported compounds N-(2,3-indolo-betulinoyl)glycine (BA3), 2,3-indolo-betulinic acid (BA4), and BI. These compounds were evaluated for their effects on murine melanoma cells (B164A5) using various in vitro assays. The introduction of an indole framework at the C2 position of BI resulted in an increased cytotoxicity. Furthermore, the cytotoxicity of compound BA4 was enhanced by conjugating its carboxylic group with an amino acid residue. BA2 and BA3, with glycine and glycylglycine residues at C28, exhibited approximately 2.20-fold higher inhibitory activity compared to BA4. The safety assessment of the compounds on human keratinocytes (HaCaT) has revealed that concentrations up to 10 µM slightly reduced cell viability, while concentrations of 75 µM resulted in lower cell viability rates. LDH leakage assays confirmed cell membrane damage in B164A5 cells when exposed to the tested compounds. BA2 and BA3 exhibited the highest LDH release, indicating their strong cytotoxicity. The NR assay revealed dose-dependent lysosome disruption for BI and 2,3-indolo-betulinic acid derivatives, with BA1, BA2, and BA3 showing the most cytotoxic effects. Scratch assays demonstrated concentration-dependent inhibition of cell migration, with BA2 and BA3 being the most effective. Hoechst 3342 staining revealed that BA2 induced apoptosis, while BA3 induced necrosis at lower concentrations, confirming their anti-melanoma properties. In conclusion, the semisynthetic derivatives of BI, particularly BA2 and BA3, show promise as potential candidates for further research in developing effective anti-cancer therapies.

Evaluation of the Astragalus exscapus L. subsp. transsilvanicus Roots' Chemical Profile, Phenolic Composition and Biological Activities.

Novel and natural molecules for pharmaceutical applications are a contemporary preoccupation in science which prompts research in underexplored environments. Astragalus exscapus ssp. transsilvanicus (Schur) Nyár. (ASTRA) is a plant species endemic to Transylvania, having a very similar root system with that of A. membranaceus (Fisch.) Bunge, known for its health promoting properties. The present study endeavored to perform basic characterization of the ASTRA roots by proximate analysis, to investigate the fatty acid profile of the lipids extracted from the ASTRA roots, to examine the phenolic composition of the root extracts by liquid chromatography, and to evaluate the biological activities through determination of the antioxidant, antimicrobial and cytotoxic capacities of the extracts. The primary compounds found in the ASTRA roots were carbohydrates and lipids, and the fatty acid composition determined by GC-MS showed linoleic acid as preponderant compound with 31.10%, followed by palmitic, oleic and α-linolenic acids with 17.30%, 15.61% and 14.21%, respectively. The methanol extract of the ASTRA roots presented highest phenolic content, Astragaloside IV being the predominant compound with 425.32 ± 0.06 µg/g DW. The antimicrobial assay showed remarkable antimicrobial potential of the extract at a concentration of 0.356 and 0.703 mg ASTRA root powder (DW)/mL, highlighting its efficacy to inhibit S. aureus and S. epidermidis bacterial strains. Furthermore, the cell proliferation assessment showed the noteworthy proficiency of the treatment in inhibiting the proliferation of B16F10 melanoma cells.

Phytochemical Profile and Selective Cytotoxic Activity of a Solanum bulbocastanum Dun. Methanolic Extract on Breast Cancer Cells.

Solanum bulbocastanum is a wild potato species, intensively used in potato breeding programs due to its resistance to environmental factors. Thus, its biochemical profile and putative human health-related traits might be transferred into potato cultivars aimed for consumption. This study aims to assess the phytochemical profile and the selective cytotoxicity of an S. bulbocastanum extract against breast cancer cells. Dry leaves were subjected to ultrasonication-assisted extraction in methanol [70%]. The phenolic and glycoalkaloid profiles were determined by HPLC-PDA/-ESI+-MS. The volatile profile was investigated by nontargeted ITEX/GC-MS. The extract was tested against three breast cancer cell lines (MCF7, MDA-MB-231, HS578T) and a healthy cell line (HUVEC) by the MTT assay, to assess its selective cytotoxicity. The phenolic profile of the extract revealed high levels of phenolic acids (5959.615 µg/mL extract), and the presence of flavanols (818.919 µg/mL extract). The diversity of the volatile compounds was rather low (nine compounds), whereas no glycoalkaloids were identified, only two alkaloid precursors (813.524 µg/mL extract). The extract proved to be cytotoxic towards all breast cancer cell lines (IC50 values between 139.1 and 356,1 µg/mL), with selectivity coefficients between 1.96 and 4.96 when compared with its toxicity on HUVECs. Based on these results we conclude that the exerted cytotoxic activity of the extract is due to its high polyphenolic content, whereas the lack of Solanaceae-specific glycoalkaloids might be responsible for its high selectivity against breast cancer cells in comparison with other extract obtained from wild Solanum species. However, further research is needed in order to assess the cytotoxicity of the individual compounds found in the extract, as well as the anti-tumor potential of the S. bulbocastanum tubers.

Green Synthesis of Silver Nanoparticles Using Populi gemmae Extract: Preparation, Physicochemical Characterization, Antimicrobial Potential and In Vitro Antiproliferative Assessment.

Green route is an economic, facile and eco-friendly method, employed for the synthesis of various types of nanoparticles, having it as a starting point biological entity, especially as a plant extract. The present study aims to obtain silver nanoparticles (AgNPs) starting from an ethanolic extract of Populi gemmae (Pg), by adjusting the reaction parameters. The morphological and structural characterization exhibited that both the reaction temperature and the concentration of metal salt, contributes to the obtaining of Pg-AgNPs with adjustable size and shape. The newly synthesized nanoparticles exhibited a good antibacterial activity on Gram-positive bacteria as well as antifungal activity. The in vitro antiproliferative activity of Pg-AgNPs was assessed on two different cancer cell lines (breast cancer cells-MCF7 and lung carcinoma epithelial cells-A549). Results have shown that the green-synthetized Pg-AgNPs_S2 (obtained at 60 °C, using AgNO3 of 5 M) induced a substantial decrease in tumor cell viability in a dose-dependent manner with an IC50 ranging from 5.03 to 5.07 µg/mL on A549 cell line and 3.24 to 4.93 µg/mL on MCF7 cell line.

Antimicrobial activity, in vitro anticancer effect (MCF-7 breast cancer cell line), antiangiogenic and immunomodulatory potentials of Populus nigra L. buds extract.

PURPOSE: The aim of this study was to evaluate the antioxidant potential, antimicrobial activity, the in vitro anticancer effect (tested on MCF-7 breast cancer cell line), as well as the antiangiogenic and immunomodulatory potential of Populus nigra L. bud (Pg) extract collected from the western part of Romania. RESULTS: Populus nigra L. bud extract presents an important antioxidant activity, due to the rich phytochemical composition. Regarding the biological activity, results have shown that poplar bud extract presents a significant inhibitory activity against Gram-positive bacteria and a dose-dependent decrease of MCF-7 tumor cell viability with an IC50 of 66.26 µg/mL, while not affecting healthy cells. Phenomena of early apoptotic events at the maximum concentration tested (150 µg/mL) were detected by Annexin V-PI double staining. The extract induced G0/G1 phase cell cycle arrest. In addition, Pg extract showed antiangiogenic potential on the chorioallantoic membrane. Also, at the highest concentration (150 µg/mL), good tolerability and no signs of toxicity upon vascular plexus were observed. Moreover, in low concentrations, the Pg extract had immunomodulatory activity on primary human dendritic cells by upregulating IL-12 and IL-23 subunits. CONCLUSION: The study concludes that poplar bud extract elicited antioxidant activity, antitumor properties on the breast cancer cell line, followed by an antiangiogenic effect and an immunomodulatory potential on human primary dendritic cells. The biological activity of Populus nigra L. buds extract may open new directions of research on the topic addressed.

Anthocyanins: Metabolic Digestion, Bioavailability, Therapeutic Effects, Current Pharmaceutical/Industrial Use, and Innovation Potential.

In this work, various concepts and features of anthocyanins have been comprehensively reviewed, taking the benefits of the scientific publications released mainly within the last five years. Within the paper, common topics such as anthocyanin chemistry and occurrence, including the biosynthesis of anthocyanins emphasizing the anthocyanin formation pathway, anthocyanin chemistry, and factors influencing the anthocyanins' stability, are covered in detail. By evaluating the recent in vitro and human experimental studies on the absorption and bioavailability of anthocyanins present in typical food and beverages, this review elucidates the significant variations in biokinetic parameters based on the model, anthocyanin source, and dose, allowing us to make basic assumptions about their bioavailability. Additionally, special attention is paid to other topics, such as the therapeutic effects of anthocyanins. Reviewing the recent in vitro, in vivo, and epidemiological studies on the therapeutic potential of anthocyanins against various diseases permits a demonstration of the promising efficacy of different anthocyanin sources at various levels, including the neuroprotective, cardioprotective, antidiabetic, antiobesity, and anticancer effects. Additionally, the studies on using plant-based anthocyanins as coloring food mediums are extensively investigated in this paper, revealing the successful use of anthocyanins in coloring various products, such as dietary and bakery products, mixes, juices, candies, beverages, ice cream, and jams. Lastly, the successful application of anthocyanins as prebiotic ingredients, the innovation potential of anthocyanins in industry, and sustainable sources of anthocyanins, including a quantitative research literature and database analysis, is performed.

Novel Delivery Systems of Polyphenols and Their Potential Health Benefits.

Liposome-based delivery systems have been studied and used more frequently in recent years due to their advantages, such as low toxicity, specificity, and the ability to protect the encapsulated substance from environmental factors, which could otherwise degrade the active compound and reduce its effectiveness. Given these benefits, many researchers have encapsulated polyphenols in liposomes, thus increasing their bioavailability and stability. Similarly, polyphenols encapsulated in liposomes are known to produce more substantial effects on targeted cells than unencapsulated polyphenols, while having minimal cytotoxicity in healthy cells. Although polyphenols play a role in preventing many types of disease and generally have beneficial effects on health, we solely focused on their chemopreventive effects on cancer through liposomes in this review. Our goal was to summarize the applicability and efficacy of liposomes encapsulated with different classes of polyphenols on several types of cancer, thus opening the opportunity for future studies based on these drug delivery systems.

Recent Advances in Phenolic Metabolites and Skin Cancer.

Skin cancer represents any tumor development from the cutaneous structures within the epidermis, dermis or subcutaneous tissue, and is considered to be the most prevalent type of cancer. Compared to other types of cancer, skin cancer is proven to have a positive growth rate of prevalence and mortality. There are available various treatments, including chemotherapy, immunotherapy, radiotherapy and targeted therapy, but because of the multidrug resistance development, a low success has been registered. By this, the importance of studying naturally occurring compounds that are both safe and effective in the chemoprevention of skin cancer is emphasized. This review focuses on melanoma because it is the deadliest form of skin cancer, with a significantly increasing incidence in the last decades. As chemopreventive agents, we present polyphenols and their antioxidant activity, anti-inflammatory effect, their ability to balance the cell cycle and to induce apoptosis and their various other effects on skin melanoma. Besides chemoprevention, studies suggest that polyphenols can have treating abilities in some conditions. The limitations of using polyphenols are also pointed out, which are related to their poor bioavailability and stability, but as the technology is well developed, it is possible to augment the efficacy of polyphenols in the case of melanoma.

Extracts of the Wild Potato Species Solanum chacoense on Breast Cancer Cells: Biochemical Characterization, In Vitro Selective Cytotoxicity and Molecular Effects.

Solanum chacoense (wild potato) is intensively used in breeding, its biochemical profile and putative human health-related traits being transferred into potato cultivars aimed for consumption. The goal of this study was to evaluate the biochemical profile and the anti-tumor potential of methanolic extracts obtained from S. chacoense leaves and tubers against three breast cancer cell lines in comparison to healthy endothelial cells (HUVEC). The biochemical profile of the extracts was determined by HPLC-PDA/-ESI+-MS and ITEX/GC-MS, the selective cytotoxicity by MTT assay whereas RT-qPCR was used to evaluate the expression of proliferation- and apoptosis-related genes. Both extracts proved to be rich in phenolic acids and volatile compounds, the leaf extract also containing glycoalkaloids. Both extracts proved to be cytotoxic for breast cancer cell lines, with IC50 values varying between 132.9 and 390.7 µg/ml. Both extracts had selective cytotoxicity against MCF7 cell line in comparison to HUVECs (selectivity coefficients >2.3). The treatment with the extracts induced overexpression of the pro-apoptotic gene BAX¸ down-regulation of the anti-apoptotic gene BCL-2 and the pro-proliferation genes NFkB, CCND1, and STAT3. Thus S. chacoense extracts proved to be rich in compounds with anticancer proprieties and are capable of inducing selective cytotoxicity on MCF7 cell line.

Botanical Therapeutics (Part II): Antimicrobial and In Vitro Anticancer Activity against MCF7 Human Breast Cancer Cells of Chamomile, Parsley and Celery Alcoholic Extracts.

BACKGROUND: This study was designed as a continuation of a complex investigation about the phytochemical composition and biological activity of chamomile, parsley, and celery extracts against A375 human melanoma and dendritic cells. OBJECTIVE: The main aim was the evaluation of the antimicrobial potential of selected extracts as well as the in vitro anticancer activity against MCF7 human breast cancer cells. METHODS: In order to complete the picture regarding the phytochemical composition, molecular fingerprint was sketched out by the help of FTIR spectroscopy. The activity of two enzymes (acetylcholinesterase and butyrylcholinesterase) after incubation with the three extracts was spectrophotometrically assessed. The antimicrobial potential was evaluated by disk diffusion method. The in vitro anticancer potential against MCF7 human breast cancer cells was appraised by MTT, LDH, wound healing, cell cycle, DAPI, Annexin-V-PI assays. RESULTS: The results showed variations between the investigated extracts in terms of inhibitory activity against enzymes, such as acetyl- and butyrilcholinesterase. Chamomile and parsley extracts were active only against tested Gram-positive cocci, while all tested extracts displayed antifungal effects. Among the screened samples at the highest tested concentration, namely 60µg/mL, parsley was the most active extract in terms of reducing the viability of MCF7 - human breast adenocarcinoma cell line and inducing the release of lactate dehydrogenase. On the other hand, chamomile and celery extracts manifested potent anti-migratory effects. Furthermore, celery extract was the most active in terms of total apoptotic events, while chamomile extract induced the highest necrosis rate. CONCLUSION: The screened samples containing phytochemicals belonging in majority to the class of flavonoids and polyphenols can represent candidates for antimicrobial and anticancer agents.

A Recent Insight Regarding the Phytochemistry and Bioactivity of Origanum vulgare L. Essential Oil.

Origanum vulgare L. is a widely used aromatic plant, especially due to its content in essential oil, mainly rich in carvacrol and thymol. The ethnopharmacological uses of Origanum vulgare L. essential oil (OEO) comprise digestive, respiratory, or dermatological disorders. The review focuses on the increasing number of recent studies investigating several biological activities of OEO. The bioactivities are in tight relation to the phytochemical profile of the essential oil, and also depend on taxonomic, climatic, and geographical characteristics of the plant material. The antibacterial, antifungal, antiparasitic, antioxidant, anti-inflammatory, antitumor, skin disorders beneficial effects, next to antihyperglycemic and anti-Alzheimer activities were reported and confirmed in multiple studies. Moreover, recent studies indicate a positive impact on skin disorders of OEO formulated as nanocarrier systems in order to improve its bioavailability and, thus, enhancing its therapeutic benefits. The review brings an up to date regarding the phytochemistry and bioactivity of Origanum vulgare L. essential oil, underlining also the most successful pharmaceutical formulation used for skin disorders.

An Overview of Gut Microbiota and Colon Diseases with a Focus on Adenomatous Colon Polyps.

It is known and accepted that the gut microbiota composition of an organism has an impact on its health. Many studies deal with this topic, the majority discussing gastrointestinal health. Adenomatous colon polyps have a high prevalence as colon cancer precursors, but in many cases, they are hard to diagnose in their early stages. Gut microbiota composition correlated with the presence of adenomatous colon polyps may be a noninvasive and efficient tool for diagnosis with a high impact on human wellbeing and favorable health care costs. This review is meant to analyze the gut microbiota correlated with the presence of adenomatous colon polyps as the first step for early diagnosis, prophylaxis, and treatment.

Biological Evaluation of Black Chokeberry Extract Free and Embedded in Two Mesoporous Silica-Type Matrices.

Black chokeberry fruits possess a wide range of biological activities, among which the most important that are frequently mentioned in the literature are their antioxidant, anti-inflammatory, anti-proliferative, and antimicrobial properties. The present paper reports, for the first time, the encapsulation of the ethanolic extract of Aronia melanocarpa L. fruits into two mesoporous silica-type matrices (i.e., pristine MCM-41 and MCM-41 silica decorated with zinc oxide nanoparticles). The aim of this work was to evaluate the antiradicalic capacity, the antimicrobial potential, and the effects on the cell viability on a cancer cell line (i.e., A375 human melanoma cell line) versus normal cells (i.e., HaCaT human keratinocytes) of black chokeberry extract loaded on silica-type matrices in comparison to that of the extract alone. The ethanolic polyphenolic extract obtained by conventional extraction was characterized by high-performance liquid chromatography with a photodiode array detector (HPLC-PDA) and spectrophotometric methods. The extract was found to contain high amounts of polyphenols and flavonoids, as well as good radical scavenging activity. The extract-loaded materials were investigated by Fourier transform infrared spectroscopy, N2 adsorption-desorption isotherms, thermal analysis, and radical scavenger activity on solid samples. The black chokeberry extract, both free and loaded onto mesoporous silica-type matrices, exhibited a significant antioxidant capacity. Antibacterial activity was recorded only for Gram-positive bacteria, with a more potent antibacterial effect being observed for the extract loaded onto the ZnO-modified MCM-41 silica-type support than for the free extract, probably due to the synergistic effect of the ZnO nanoparticles that decorate the pore walls of silica. The cellular viability test (i.e., MTT assay) showed dose- and time-dependent activity regarding the melanoma cell line. The healthy cells were less affected than the cancer cells, with all tested samples showing good cytocompatibility at doses of up to 100 µg/mL. Improved in vitro antiproliferative and antimigratory (i.e., scratch assay) potential was demonstrated through the loading of black chokeberry extract into mesoporous silica-type matrices, and the screened samples exhibited low selectivity against the tested non-tumor cell line. Based on presented results, one can conclude that mesoporous silica-type matrices are good hosts for black chokeberry extract, increasing its antioxidant, antibacterial (on the screened strains), and in vitro antitumor (on the screened cell line) properties.

Cannabidiol-from Plant to Human Body: A Promising Bioactive Molecule with Multi-Target Effects in Cancer.

Cannabis sativa L. is a plant long used for its textile fibers, seed oil, and oleoresin with medicinal and psychoactive properties. It is the main source of phytocannabinoids, with over 100 compounds detected so far. In recent years, a lot of attention has been given to the main phytochemicals present in Cannabis sativa L., namely, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). Compared to THC, CBD has non-psychoactive effects, an advantage for clinical applications of anti-tumor benefits. The review is designed to provide an update regarding the multi-target effects of CBD in different types of cancer. The main focus is on the latest in vitro and in vivo studies that present data regarding the anti-proliferative, pro-apoptotic, cytotoxic, anti-invasive, anti-antiangiogenic, anti-inflammatory, and immunomodulatory properties of CBD together with their mechanisms of action. The latest clinical evidence of the anticancer effects of CBD is also outlined. Moreover, the main aspects of the pharmacological and toxicological profiles are given.

Melanoma Inhibition by Anthocyanins Is Associated with the Reduction of Oxidative Stress Biomarkers and Changes in Mitochondrial Membrane Potential.

Anthocyanins are water soluble pigments which have been proved to exhibit health benefits. Several studies have investigated their effects on several types of cancer, but little attention has been given to melanoma. The phytochemical content of nine different berry samples was assessed by liquid chromatography followed by electrospray ionization mass spectrometry (LC-ESI+-MS). Twenty-six anthocyanins were identified, after a previous C18 Sep-pak clean-up procedure. Chokeberry and red grape anthocyanins rich extracts (C-ARE and RG-ARE) were selected to be tested on normal and melanoma cell lines, due to their different chemical pattern. C-ARE composition consists of cyanidin aglycone glycosylated with different sugars; while RG-ARE contains glucosylated derivatives of five different aglycones. Both C-ARE and RG-ARE anthocyanins reduced proliferation, increased oxidative stress biomarkers and diminished mitochondrial membrane potential in melanoma cells, having no negative influence on normal cells. A synergistic response may be attributed to the five different aglycones present in RG-ARE, which proved to exert greater effects on melanoma cells than the mixture of cyanidin derivatives with different sugars (C-ARE). In conclusion, C-ARE and RG-ARE anthocyanins may inhibit melanoma cell proliferation and increase the level of oxidative stress, with opposite effect on normal cells. Therefore, anthocyanins might be recommended as active ingredients for cosmetic and nutraceutical industry. Graphical Abstract ᅟ.

Antiproliferative and Apoptotic Potential of Cyanidin-Based Anthocyanins on Melanoma Cells.

Elderberries are known for their high anthocyanins content, which have been shown to possess anti-proliferative and anti-cancer effects. Anthocyanins enriched extract (AEE) was obtained from elderberries and was characterized by LC/DAD/ESI-MS analysis. Five cyanidin-based anthocyanins were identified, among which Cy-3-O-samb was the major compound (51%). The total anthocyanins content of AEE was 495 mg Cy-3-O-samb/100 g FW. AEE inhibited proliferation of metastatic B16-F10 murine melanoma cells, in a concentration-dependent manner, with an IC50 of 264.3 µg/mL. LDH (lactate dehydrogenase), as a marker of membrane integrity, increased 74% in B16-F10 cells treated with 250 µg/mL AEE, compared to control. It was observed that apoptosis is the mechanism of melanoma cell death after AEE treatment, confirmed morphologically by acridine orange/ethidium bromide double staining and TUNEL analysis. These results indicate that elderberry-derived anthocyanins might be utilized in future applications as topical adjuvant in skin cancer therapy.

Chokeberry Anthocyanin Extract as Pancreatic ß-Cell Protectors in Two Models of Induced Oxidative Stress.

The aim of this study was to investigate the protective effects of a chokeberry anthocyanin extract (CAE) on pancreatic ß-cells (ßTC3) exposed to hydrogen peroxide- (H2O2-) and high glucose- (HG-) induced oxidative stress conditions. In order to quantify individual anthocyanins high performance liquid chromatography (HPLC) coupled to photodiode array (PDA) was used. The identification of the fragment ion pattern of anthocyanins was carried out by electrospray ionization mass spectrometry (LC-ESI-MS). The results showed that physiologically achievable concentrations of CAE (1, 5, and 10 µM) protect ßTC3 against H2O2- and HG-induced cytotoxicity. Antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were increased in pancreatic ß-cells pretreated with CAE compared to cells exposed to the prooxidant agents. GSH levels initially reduced after exposure to H2O2 and HG were restored by pretreatment with CAE. Insulin secretion in ßTC3 cells was enhanced by CAE pretreatment. CAE restored the insulin pool and diminished the intracellular reactive oxygen species level in glucose-induced stress condition in ßTC3 cells. These results demonstrate that anthocyanins from CAE were biologically active, showing a secretagogue potential and an antioxidative protection of enzymatic systems, conferring protection against H2O2 and glucose toxicity in ßTC3 cells.

Antiproliferative and antioxidant properties of anthocyanin rich extracts from blueberry and blackcurrant juice.

The present study was aimed at evaluating the antiproliferative potential of anthocyanin-rich fractions (ARFs) obtained from two commercially available juices (blueberry and blackcurrant juices) on three tumor cell lines; B16F10 (murine melanoma), A2780 (ovarian cancer) and HeLa (cervical cancer). Individual anthocyanin determination, identification and quantification were done using HPLC-MS. Antioxidant activity of the juices was determined through different mechanism methods such as DPPH and ORAC. For biological testing, the juices were purified through C18 cartridges in order to obtain fractions rich in anthocyanins. The major anthocyanins identified were glycosylated cyanidin derivatives. The antiproliferative activity of the fractions was tested using the MTT assay. The antiproliferative potential of ARF was found to be associated with those bioactive molecules, anthocyanins due to their antioxidant potential. The results obtained indicated that both blueberry and blackcurrants are rich sources of antioxidants including anthocyanins and therefore these fruits are highly recommended for daily consumption to prevent numerous degenerative diseases.